Positron emission tomography (PET) with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) is effective for monitoring head and neck cancer. However, lack of anatomic landmarks, variable physiologic FDG uptake, and asymmetric FDG distribution in the neck can confound image interpretation. This is particularly true in the treated neck, where distortion of normal tissue planes makes detection of early disease recurrence difficult with conventional computed tomography (CT) and magnetic resonance imaging. Combined PET-CT helps prevent the misinterpretation of FDG PET findings in patients with head and neck cancer. Superior localization of FDG uptake with this technique can improve diagnostic accuracy and help avoid interpretative pitfalls. In the future, development of tumor-specific ligands will enhance the usefulness of PET-CT in the detection of initial tumors and tumor recurrence, in the evaluation of tumors with low FDG avidity, and in treatment targeting. Furthermore, improved scanner resolution will help address the limitations of PET-CT with respect to small lesions and may make this modality more valuable in initial tumor staging.